The "Jennerian" approach to vaccination, which involves the use of a live virus vaccine strain derived from a non-human host, has been evaluated in clinical trials using surrogate rotavirus strains of bovine origin (by others) or of simian [rhesus monkey] origin (by the Epidemiology Section, LID). This strategy has had limited success because serotype-specific immunity against each of the four epidemiologically important human rotavirus VP7 serotypes could not be achieved consistently in infants less than 6 months of age who had not undergone prior rotavirus infection. Protection was observed when the rhesus rotavirus (RRV) vaccine (VP7 serotype 3) was used to immunize young infants who later were naturally exposed to human rotavirus strains of the same VP7 serotype. However, in other trials in which rotavirus with a VP7 serotype 1 predominated in the community, vaccine efficacy was variable. Thus, most recent clinical trials have employed a "modified Jennerian" approach in which individual reassortant strains initially and later a quadrivalent vaccine of broader antigenic coverage (that includes viruses of VP7 serotype 1, 2, 3, and 4) was used for immunization. This vaccine contains RRV (serotype 3) and reassortant rotaviruses containing 10 RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity. Encouraging but variable results have been observed in efficacy trials with individual reassortant vaccines. In collaborative studies, in a field trial in Finland where VP7 serotype 1 strains were predominantly, the protective efficacy of a reassortant vaccine with VP7 serotype 1 specificity was moderately high in the first but not the second rotavirus "season," whereas that of a reassortant vaccine with VP7 serotype 2 specificity was moderately high for both "seasons." Vaccine efficacy was observed only in individuals who developed a seroresponse after vaccination. The heterotypic protection was unexpected and is under investigation. Further successes as well as failures of this approach were observed in other locations. Analysis of the efficacy of the quadrivalent vaccine are in progress. In addition, a naturally attenuated human rotavirus strain, M37, with a VP7 specificity of serotype 1 and a unique VP4 specificity shared by other neonatal strains belonging to VP7 serotype 1, 2, 3, or 4, is also under evaluation. Phase 1 trials of the human rotavirus M37 live vaccine have been completed successfully. In a preliminary phase II trial in Finland this vaccine failed to induce protection.